Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients

NCT ID: NCT01114529

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 828 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-09
• Study Completion Date: 2014-10-30

Brief Summary

The purpose of this study was to determine whether an early Calcineurin Inhibitor (CNI) to everolimus conversion at 10-14 weeks post transplantation improves renal allograft function without compromising efficacy compared to standard CNI treatment in de novo renal allograft recipients. In addition, the study was designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients

Detailed Description

This was a 24-month, multi-center, randomized, open-label trial with two parallel arms in adult de novo renal allograft recipients. The study consisted of a run-in period from transplantation to Randomization and a treatment period from Randomization until Month 24. At baseline visit, patients were transplanted and entered the run-in period from transplantation (Baseline) to Randomization (week 10-14 post-transplantation). At Week 10-14, eligible patients were randomized into one of the 2 treatment arms: standard CNIs and Myfortic versus everolimus and Myfortic and entered the treatment period of the study from Randomization to Month 24. Patients in both arms received steroids as per center practice and in any caseat least 5 mg/Day. At Randomization, patients were stratified according to their renal allograft function and previous cardiovascular events. The main analysis was performed at Month 12 and the follow-up analysis was performed at Month 24.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus

Conversion from CNI to everolimus in combination with Myfortic and steroids

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Early CNI to everolimus conversion

Calcineurin inhibitor, Prograf or Neoral

Control arm: CNI continuation, either Prograf or Neoral in combination with Myfortic and steroids

Group Type: ACTIVE_COMPARATOR

Prograf or Neoral

Intervention Type: DRUG

Active CNI-based control (Prograf or Neoral)

Interventions

Everolimus

Early CNI to everolimus conversion

Intervention Type: DRUG

Prograf or Neoral

Active CNI-based control (Prograf or Neoral)

Intervention Type: DRUG

Other Intervention Names

Certican, Zortress, RAD001; Tacrolimus or Cyclosporine

Eligibility Criteria

Inclusion Criteria

• Male or female renal allograft recipients at least 18 years old.
• Written informed consent.
• Patient receiving a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor.
• Cold ischemia time (CIT) < 24 hours.
• Negative pregnancy test for female patients.

• Patients on CNI (TAC or CsA) + Myfortic + steroids.
• Serum creatinine < 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) ≥ 25 mL/min/1.73m exp2 (without renal replacement therapy).

Exclusion Criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Recipient of multiple organ transplants.
• Recipient of ABO incompatible allograft or a positive cross-match.
• Panel Reactive Antibodies (PRA) level ≥ 30 %.
• Positive test for human immunodeficiency virus (HIV).
• Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor.
• HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN).
• Severe restrictive or obstructive pulmonary disorders.
• Patient with severe allergy requiring acute or chronic treatment or hypersensitivity to any of the study drugs or similar drugs.
• Severe hypercholesterolemia or hypertriglyceridemia.
• Low platelet count.
• Low white blood cell count.
• History of malignancy of any organ system

• Graft loss.
• Patient on renal replacement therapy.
• Patient who experienced severe humoral and/or cellular rejection (BANFF ≥ IIb).
• Patient with ≥ 2 episodes of AR or an AR episode that needed antibody treatment.
• Patient with ongoing or currently treated AR (2 weeks prior to randomization).
• Proteinuria > 1 g/day.
• Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).
• Low platelet count; Low white blood cell count; Low absolute neutrophil count; Low hemoglobin.
• Severe liver disease.
• Systemic infection requiring continued therapy that would interfere with the objectives of the study.
• Severe hypercholesterolemia or hypertriglyceridemia.
• Patients with ongoing wound healing problems, clinically significant infection requiring continued therapy.
• Presence of intractable immunosuppressant complications or side effects.
• Patients on anticoagulants that prevents renal allograft biopsy.
• Use of prohibited medication.
• Use of immunosuppressive agents not utilized in the protocol.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential not using a highly effective method of birth control.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

San Martín, Buenos Aires, Argentina

Novartis Investigative Site

Resistencia, Chaco Province, Argentina

Novartis Investigative Site

Córdoba, , Argentina

Novartis Investigative Site

Córdoba, , Argentina

Novartis Investigative Site

Córdoba, , Argentina

Novartis Investigative Site

Santa Fe, , Argentina

Novartis Investigative Site

Camperdown, New South Wales, Australia

Novartis Investigative Site

Adelaide, South Australia, Australia

Novartis Investigative Site

Clayton, Victoria, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Tartu, , Estonia

Novartis Investigative Site

Brest, , France

Novartis Investigative Site

Nice, , France

Novartis Investigative Site

Toulouse, , France

Novartis Investigative Site

Tours, , France

Novartis Investigative Site

Vandœuvre-lès-Nancy, , France

Novartis Investigative Site

Aachen, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Frankfurt am Main, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hannover Muenden, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Pátrai, Greece, Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Visakhapatnam, Andhra Pradesh, India

Novartis Investigative Site

Bangalore, Karnataka, India

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Novartis Investigative Site

Lucknow, Uttar Pradesh, India

Novartis Investigative Site

New Delhi, , India

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Siena, SI, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Riga, , Latvia

Novartis Investigative Site

Vilnius, , Lithuania

Novartis Investigative Site

Torreón, Coahuila, Mexico

Novartis Investigative Site

Mexico City, Mexico City, Mexico

Novartis Investigative Site

Aguascalientes, , Mexico

Novartis Investigative Site

Veracruz, , Mexico

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Groningen, , Netherlands

Novartis Investigative Site

Leiden, , Netherlands

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Carnaxide - Linda-A-Velha, Lisbon District, Portugal

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Cluj-Napoca, Jud Cluj, Romania

Novartis Investigative Site

Krasnodar, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Nizhny Novgorod, , Russia

Novartis Investigative Site

Novosibirsk, , Russia

Novartis Investigative Site

S.-Petersburg, , Russia

Novartis Investigative Site

Samara, , Russia

Novartis Investigative Site

Volzhskiy, , Russia

Novartis Investigative Site

Málaga, Andalusia, Spain

Novartis Investigative Site

Santander, Cantabria, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Novartis Investigative Site

A Coruña, Galicia, Spain

Novartis Investigative Site

Zaragoza, , Spain

Novartis Investigative Site

Khon Kaen, THA, Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Novartis Investigative Site

Büyükçekmece / Ýstanbul, , Turkey (Türkiye)

Novartis Investigative Site

Fatih / Istanbul, , Turkey (Türkiye)

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Countries

Argentina; Australia; Austria; Belgium; Estonia; France; Germany; Greece; India; Italy; Latvia; Lithuania; Mexico; Netherlands; Norway; Portugal; Romania; Russia; Spain; Thailand; Turkey (Türkiye)

Related Links

https://doi.org/10.1111/ajt.13898

The American Journal of Transplantation, Poster Abstracts, 2016

Provider: John Wiley & Sons, Ltd

Other Identifiers

2009-015918-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001A2429

Identifier Type: -

Identifier Source: org_study_id